Support is requested to continue what has proved to be a highly successful program for the training of postdoctoral fellows (M.D. and Ph.D.) in biochemical, cell biological, and molecular genetic aspects of pathobiology, and predoctoral students in a combined experimental pathology (molecular medicine and pharmacology) and biology graduate program. Historically, this program has attracted fellows who have already had formal training in diagnostic pathology or related disciplines, and who have used the opportunities provided by the training program to work on basic mechanisms of disease at the molecular level. The program has also attracted Ph.D.'s to disease-related problems. Since the expansion of the program to include predoctoral trainees during the last two competitive renewals, several of these participants have also focused their training in disease related areas. Since the inception of this program, a very high percentage of trainees have gone on to establish themselves as productive independent investigators in academic and industrial positions. Many have remained in academic pathology. During the last renewal period, an expansion of the program was sought to reflect growth in the training faculty, and to better balance support between pre- and post-doctoral candidates. This decision to seek an expansion of the predoctoral training aspects of the program reflected the success enjoyed by the innovative predoctoral program initiated by the fusion of Ph.D. programs in experimental pathology (Pathology Department) and Biology under auspices of this program four years ago. This expansion was approved by the review section, but funding for it was reduced when the award was made. Since that time, we have strengthened even further our predoctoral programs with the creation of an integrated interdisciplinary graduate program at Yale in the Biological Sciences. Given the continuing and still growing demand for basic science investigators focused on disease oriented research, with a sophisticated understanding of disease processes and pathobiology, we are again seeking an expansion of the program to the levels approved last time. At the predoctoral level, this program is available to trainees enrolled in the School of Graduate Studies of either the Yale School of Medicine (YSM) or the Faculty of Arts and Sciences (FAS). Significant contributions to the program are made by faculty in Pathology, Genetics, Molecular and Cellular Biology, and others.